Condensation of aromatic aldehydes with carbohydrates and related materials



United States Patent CONDENSATION OF AROMATIC ALDEl-IYDES TWFETH CARBOHYDRATES AND RELATED MA- Carl B. Linn, Riverside, 11]., assignor, by mesne assignments, to Universal Oil Products Company, Des Plaines, 111., a corporation of Delaware No Drawing. Application June 18, 1957 Serial No. 666,488

5 Claims. (Cl. 260--345.9)

This application is a continuation-in-part of my copending application Serial No. 401,068, filed December 29, 1953, now Patent No. 2,798,079.

This invention relates to a process for interacting aromatic aldehydes with carbohydrates and materials closely related to carbohydrates. The process relates more particularly to the condensation of simple sugars, their desoxyand omega-carboxy derivatives, compound sugars or oligosaccharides, and polysaccharides, with aromatic aldehydes in the presence of a hydrogen fluoride catalyst.

An object of this invention is to produce organic materials suitable for use per se or as intermediates in the manufacture of detergents, pharmaceuticals, explosives, resins, gelling agents, surface coatings, oxidation inhibitors, metal deactivators, etc., by condensing aromatic aldehydes with carbohydrates or with carbohydrate derivatives.

One embodiment of this invention relates to a process which comprises condensing an aromatic aldehyde with a carbohydrate in the presence of a hydrogen fluoride catalyst to produce a compound selected from the group consisting of a formylaryl-d'esoxy-alditol anda formylaryldesoxy-ketitol, and recovering said resultant condensation product.

A specific embodiment of this inventionrelates to a process which comprises condensing benzaldehyde with glucose in the presence of a hydrogen fluoride catalyst to produce a 1-(formylphenyl)-1-desoxy-glucitol, and recovering said resultant condensation product.

I have found that useful water-insoluble condensation products and also water-soluble condensation products are formed by reacting aromatic aldehydes with carbohydrates and substances related to carbohydrates in the presence of a hydrogen fluoride catalyst. These reactions may be carried out in steel equipment or other suitable apparatus lined with silver, copper, and certain alloys such as Monel metal and the like. This treatment may be eiiected at temperatures of from about 40 to about 100 C. and preferably at temperatures of from about to about +50 C. The pressure at which the reaction is carried out will vary with the reaction temperature used and the mol fractions of reactants and hydrogen fluoride catalyst present. While many of the condensation reactions are carried out at substantially atmospheric pressure, it may be desirable in certain instances and with certain reactants to carry out the reaction at pressures up to about 100 atmospheres or more. It is convenient in most instances to operate the equipment utilized at the pressure generated by the reaction mixture and the catalyst contained therein.

Aromatic aldehydes which may be used as starting materials in the process of this invention include benzaldehyde, meta-tolualdehyde, para-tolualdehyde, orthochlorobenzaldehyde, para-chlorobenzaldehyde, ortho-nitrobenzaldehyde, meta-nitrobenzaldehyde, para-nitrobenzal dehyde, ortho-aminobenzaldehyde, para-aminobenzaldehyde, salicylaldehyde, meta-hyd'roxybenzaldehyde, para- Fee hydroxybenzaldehyde, ortho-methoxybenzaldehyde, anisaldehyde, para-dimethylaminobenzaldehyde, 2,6-dichlorobenzaldehyde, ortho-bro'mobenzaldehyde, para-thymolaldehyde, 9-anthraldehyde, 2-hydroxy-3,5,6-trirnethylbenzaldehyde, homosalicylaldehyde, vanillin, 2-hydroxy-3- methoxybenzaldehyde, 2,3-dime'thoxybenzaldehyde, 3,4- dimethoxybenzaldehyde, etc.

Carbohydrates which are condensed with aromatic aldehydes in the process of the present invention to form a compound selected from the group consisting of a formylaryl-desoxy-alditol and a formyla'ryl-desoxy ketitol include simple sugars, their desoxy and .ome'g'a-carboxy derivatives, compound sugars or oligosaccharides, and polysaccharides. Simple sugars include diose's, trioses, tetroses, pentoses hexoses, heptoses, octos'es,'nonoses, and decoses. Conn pound sugars include disaccharides, trisaccharides, and tetrasaccharides. Polysaccharides include polysaccharides composed of only one type of sugar residue, polysaccharides composed of more than one type of sugar unit, polysaccharides composed of one type of uronic acid unit,

i.e., polyuronides, polysaccharides composed of aldose (pentoseor' hexose) and uronic acid units, polysaccharides containing hexose'units e'sterified with an inorganic acid, and polysaccharides containing amino sugar units.

Utilizable simple sugars include the diose, glycolaldehyde; trioses, such as glycerylaldehyde and s-dihydroxyacetone; tetroses, such as erythrose, threose, erythrulose, and apiose; the pentoses, such as arabinose, xylose, ribose, lyxose, rhamnose (a methylpentose), fucose (a methyl pentose), rhodeose (a methylpentose), dig'italose (a meth- -oxymethylpentose) ketoxylose (a k'etopentose) 2-desoxy-. ribose and 2-desoxy-methylpentose (digitoxose); hexoses, such as mannose, glucose, idose, gulose, galactos'e, talose, allose, fructose, sorbose, tagatose,and psicose; heptoses, such asglucoheptose, mannohepto'se, galacto'he'ptose, sedoheptose, mannoketoheptose, glucoheptulose and perseulose; octoses', such as glucooctose, mannooctose, and galactooctose; nonoses, such as glucononose and man nononose; and decoses such as glucodeeose. Desoxy derivatives of simple sugars are formed by the replacement of a hydroxyl substituent in a sugar with hydrogen thereby forming a methyl or methylene linkage. The desoxyq pentoses and desoxyhexoses are the most commonly oc-' curring of such compounds. The ome'ga-carboxy derivatives of simple sugars, which are suitablein the process of the present invention include tartronic semialdehyde or its tautomer, hydroxypyruvic acid; alpha-gamma-dihydroxyacetoacetic acid, threuronic acid, 4-keto-2,3,5-tri-, hydroxypentan'oic acid, xyluronic acid, S-Keto-tetrahydroxyhexanoic acids such as S-keto-allonic acid, S-ketogluconic acid, S-keto-mannonic acid, S-keto-gulonic acid, and S-kcto-galactonic acid; uronic acids containing 6 car'- bon atoms such as glucuronic acid,-mannur'onic acid, and galacturonic acid, and the 6-keto pentahydroxyheptanoic acids. The simple sugars and their omega-carboxy derivatives, as starting materials for the process of this inventiorli, may be represented by the following general formu a: I

formula, when A==H, n=1, and B=H, the compound is glycolaldehyde; when A=-H, n=1, and B=CH 0H,'

the compoundv is glycerylaldehyde; when A' H,;= nee-1,".

and B =CO OI -I, the compound is tartronic semialdehyde,

a tautomer of hydroxypyruvic acid; when A=CH OH, n=1, and B=H, the compound is s-dihydroxyacetone; when A=CH OH, 11:1, and B=CH OH, the compound is erythrulose; when A=CH OH, n=1, and B=COOH, the compound is alpha-gamma-dihydroxyacetoacetic acid; when A=H, n=2, and B=CH OH, the compound is erythrose or threose; when A=H, n=2, and B=COOH, the compound is threuronic acid; when A=CH OH, n=2, and B=CH OH, the compound is riboketose or xyloketose; when A=CH OH, n=2, and B=COOH, the compound is a 4-keto-2,3,S-trihydroxypentanoic acid; when A=H, rz=3, and B=CH OH, the compound is ribose, arabinose, xylose or lyxose; when A=H, n=3, and B=COOH, the compound is a 5 carbon atom uronic acid such as xyluronic acid; when A=CH OH, n=3, and B=CH OH, the compound is psicose, fructose, sorbose, or tagatose; when A=CH OH, n=3, and B=COOH, the compound is a 5-keto-tetrahydroxyhexanoic acid; when A=H, n=4, and B=CH OH, the compound is allose, altrose, glucose, mannose, gulose, idose, galactose, or talose; when A=H, n=4, and B=COOH, the compound is a 6 carbon atom uronic acid such as glucuronic acid, mannuronic acid, and galacturonic acid; when A=CH OH, n=4, and B=CH OH, the compounds are heptoses; and when A=CI-I OH, n'=4, and B=COOH, the compounds are 6-keto-pentahydroxyheptanoic acids.

1 The utilizable oligosaccharides or compound sugars include disaccharides such as the pentose-hexose disaccharides including glucoapiose, vicianose and primeverose; the methylpentose-hexose disaccharides including glycorhamnoside, and rutinose; and the dihexoses such as turanose, maltose, lactose, cellobiose, gentiobiose, melibiose, sucrose, and trehalose. Other compound sugars are represented by tri-saccharides such as the methylpentosehexose saccharides including rhamninose and robinose; and trihexose saccharides including rafiinose, melezitose, and gentianose. An example of a suitable tetrasaccharide is stachyose.

Various polysaccharides are also utilizable in the process of the present invention. These polysaccharides include pentosans such as araban, methylpentosans such as fucosan, and hexosans such as starch, cellulose, glycogen, inulin, mannan, galactan, lichenin, levan, dextran, and laminarin. Other polysaccharides which are composed of more than one type of sugar unit such as pentosans like araboxylan, and the hexosans like galactomannan may be used. Other utilizable polysaccharides are represented by those composed of uronic acid units and aldose units such as gum arabic, damson gum, gum tragacanth, linseed mucilage, and pectins, those composed of uronic acid units such as pectic acid and alginic acid, and those containing hexose units esterified with an inorganic acid such as certain sea weed polysaccharides like agar.

The hydrogen fluoride catalyst which is used in this process may be used in anhydrous form or diluted with water to make a hydrofluoric acid of the desired concentration. The hydrofluoric acid may also be further diluted with various inert diluents when it is desirable to operate the process of this invention with low hydrogen fluoride concentrations. Suitable inert diluents include the perfluoro derivatives of n-paraffinic hydrocarbons such as perfluoro-propane, perfluoro-n-butane, perfluoro-npentane, perfluoro-n-hexane, etc. Other suitable diluents are well known to those skilled in the art, for example, cycloparafiins such as cyclopentane or cyclohexane may be utilized. In some instances, hydrofluoric acid of from about 85 to about 100% HF concentration is desirable, and in some other instances it is most desirable to use anhydrous hydrogen fluoride as the catalyst.

The process may be carried out by slowly adding a hydrogen fluoride catalyst to a stirred mixture of aromatic aldehyde and carbohydrate or related material being subjected to reaction while maintaining the reaction temperature at from about 40' to about 100 C. by suitable cooling and/or heating means. It is often desirable or advisable to commingle the reactants and catalyst at relatively low temperatures such as from about C. to about 30 C. and then to permit the reaction mixture to warm gradually while the reactants and catalyst are stirred by suitable means such as a motor driven stirrer or other adequate mixing equipment. After the reaction has reached the desired degree of completion, the hydrogen fluoride catalyst is removed from the reaction mixture by distillation at atmospheric or lower pressures, or by passing an inert gas through the reaction mixture while maintaining it at a relatively lowtemperature. Also the entire reaction mixture and catalyst may be mixed with water or may be added to ice in order to quench the activity of the hydrogen fluoride catalyst and to permit separation of the organic reaction products and unreacted starting materials from the catalyst. The organic reaction products may also be separated from aqueous hydrogen fluoride by means of an organic solvent such as ether, in which some of the organic materials may be dissolved. Further means of isolating the reaction prodnets are illustrated in the examples. Thus the product formed by reacting benzaldehyde with glucose or cellulose in the presence of substantially anhydrous hydrogen fluoride at 30 C. separated into an ether-soluble and water-insoluble product and an ether-insoluble and watersoluble product.

The process of this invention broadly emphasizes the reaction of carbohydrates including simple sugars, their derivatives, compound sugars, and polysaccharides with aromatic aldehydes using as a catalyst hydrogen fluoride. The type of product obtained is markedly affected by the length of time that the reactants are in contact with the hydrogen fluoride catalyst as well as the temperature of the reaction. The reaction products of this process lead to materials having diversified uses. For example, some of the reaction products can be used per se as surface coating materials as, for example, thermosetting resins which can be prepared simply by heating. Resins can also be made by heating the reaction products with phenol, aniline, etc., and combinations of these compounds. Nitration of many of the reaction products will give explosives. These explosives will contain nitro groups attached to the aromatic rings as well as being nitric acid esters or nitro-alcohol derivatives. Various reaction products are eflective for gelling paraflinic or aromatic hydrocarbons. mediates in the preparation of other organic compounds, for example, they may be reacted with primary amines to form Schifis bases which have utility as metal deactivators. The nature of this invention is illustrated further by the following examples, which however, should not be construed to limit unduly the generally broad scope of this invention.-

Example I This example illustrates the reaction of an aromatic aldehyde, namely benzaldehyde, with a carbohydrate, namely cellulose which is a polysaccharide containing glucoside linkages.

As an example of the manner of conducting these experiments, the following detailed description is given; In a one liter steel turbomixer autoclave is sealed 41' grams of cellulose and 68 grams of benzaldehyde. With stirring, the autoclave is cooled to 78 C. and about 220 grams of hydrogen fluoride is added. The temperature is allowed to rise to 0 C. and the reactants are then contacted at this temperature for 36 hours. Then, a stream of nitrogen is passed through the reactor at room temperature to remove most of the hydrogen fluoride. A substantial amount of hydrogen fluoride remains behind in the reaction mixture, although most of it can be removed by prolonging the nitrogen purge. The autoclave is opened and the product is found to be a heavy fuming brown syrup. This is then poured into a silver dish and depending upon the amount of hydrogen The products are useful inter-.

fluoride remaining therein weighs from about 120 to about 140 grams. After standin for several days in a hooddraft the product solidifies and is then mascerated with large quantities of cold water to remove unreacted carbohydrate, if any. The cold water insoluble portion of the product is treated with boiling water which after cooling and reduction in volume yields a chemical individual corresponding to 1,l-di-(formylphenyl)-1-desoxyglucitol of the following formula:

The product may be recrystallized from a 50% ethanol solution.

Example II This experiment again illustrates the reaction of a carbohydrate, namely glucose, with an aromatic aldehyde. In this example, 40 grams of glucose, 68 grams of benzaldehyde, and about 225 grams of hydrogen fluoride are utilized. The procedure utilized in this example is the same as that described hereinabove in Example I down through allowing the product to stand in a draft. To this crude product is added one liter of ethyl ether and the mixture is allowed to stand for two days. The ether is then decanted off and the residue is dissolved in 500 m1. of 50% hot ethanol. This alcohol solution is filtered while hot and is then allowed to stand at 0 C. The material which separates at this point corresponds to the l,l-di-(formylphenyl)-l-desoxy-glucitol described in Example I.

The more soluble part of the product is believed to contain a mono-formy1phenyl-desoxy-glucitol corresponding to the following structural formula:

CHOH (ilHOH JHOH Ha.

HzOH

Example III perature of the autoclave is then allowed to rise to room temperature and is kept there for 12 hours during which time the mixture is stirred. Then, while continuing the stirring, a stream of nitrogen is passed through the autoclave for about 3 hours. The reaction product is washed with several portions of cold water, and the cold water insoluble portion thereof isdissolv'e d in boiling water;

The hot aqueous solution is filtered, and set aside to cool. After standing for about 24 hours at about 0' C., crystals of a chemical individual are recovered therefrom. This material after recrystallization is found to have the following structural formula; r

en; me.

Example IV during which time the reaction mixture is stirred continually. Then, a stream of nitrogen is passed through the autoclave for about 6 hours. The reaction product is washed with several portions of cold water, and the cold water insoluble portion thereof is dissolved in boiling water. This hot aqueous solution is filtered, cooled, and set aside at 0 C. From this cold filtrate a new chemical entity is recovered. After recrystallization from 50% ethanol a product is isolated of the following structural formula:

O O 11-h ("3-H JHOH JHOH C lHOH l/HOE 3112011 I claim as my invention:

1. A process which comprises reacting an aromatic aldehyde selected from the group consisting of benzaldehyde and ring substituted methyl, halo, nitro, amino, hydroxy and methoxy benzaldehyde with a carbohydrate selected from the group consisting of monosaccharides, oligosaccharides, and polysaccharides, in the presence of hydrogen fluoride catalyst at a temperature of from about -40 C. to about C.

2. A process which comprises reacting benzaldehyde with cellulose in the presence of hydrogen fluoride catalyst at a temperature of from about- 40 C. to about 100 C.

3. A process which comprises reacting benzaldehyde with glucose in the presence of hydrogen fluoride catalyst at a temperature of from about -40 C. to about References Cited in the file of this patent 100 C. i

4. A process which comprises reacting ortho-tolualde- UNITED STATES PATENTS hyde with glucose in the presence of hydrogen fluoride 2,252,725 Nlederl 19, 1941 catalyst at a temperature of from about 40 C. to 5 2,798,079 Lulu y 1957 about 100 C.

5. A process which comprises reacting alpha-naphthoic OTHER REFERENCES aldehyde with starch in the presence of hydrogen fluoride Hackhs Chemical Dictionary, p. 260, 3rd Ed., The

catalyst at a temperature of from about -40 C. to Blakiston Co., Philadelphia (1944). about 100 C. 

1. A PROCESS WHICH COMPRISES REACTING AN AROMATIC ALDEHYDE SELECTED FROM THE GROUP CONSISTING OF BENZALDEHYDE AND RING SUBSTITUTED METHLY, HALO, NITRO, AMINO, HYDROXY AND METHOXY BENZALDEHYDE WITH A CARBOHYDRATE SELECTED FROM THE GROUP CONSISTING OF MONOSACCHARIDES, OLIGOSACCHARIDES, AND POLYSACCHARIDES, IN THE PRESENCE OF HYDROGEN FLUORIDE CATALYST AT A TEMPERATURE OF FROM ABOUT -40*C. TO ABOUT 100*C. 